(1) Field of the Invention
The present invention relates to a process for the preparation of cyclopentanoids particularly prostaglandins of the PGE.sub.2 class. In particular the present invention relates to a process which utilizes a novel triply convergent synthetic technique to produce prostanoid stereoisomers in pure form using three separately prepared intermediates.
(2) Prior Art
The prostaglandins are described in detail in an excellent review found in Kirk Othmer Supplement 711-752 (1984). This reference also describes some known processes for the synthesis of these compounds, particularly the Corey process. This synthesis, which is lengthy and expensive, produces PGE.sub.2 and analogs thereof in relatively low overall yield. The other synthetic processes described in this reference are related to the Corey synthesis. Noyori, R. et al Angew. Chem., Int. Ed., Engl. 23, 847 (1984) describes a process which is triply convergent but not particularly efficient.
The various prior art processes use separate protective measures for the C-11 hydroxyl group and for insuring attachment of the requisite chain at C-8 of the cyclopentane ring in preparing the PGE.sub.2 prostaglandins. A process has not been described by those skilled in the art wherein a protective group can be provided to protect the C-11 hydroxyl group and at the same time protect against undesirable reactions eminating from deprotonation at C-10 in a reactive cyclopentene intermediate containing 8-12 unsaturation by means of a cyclopentene intermediate having the formula: ##STR3## wherein R and R'C together with the C-10 oxygen provide a protective group.
Dugger at an American Chemical Society meeting in Washington, D.C. in September of 1983 (Abstract 129) discussed the preparation of an acetal protected optically active cyclopentanoid but found that the compounds were too difficult to obtain and abandoned the synthesis. The suggestion in the abstract was that various cyclopentanoid derivatives might be prepared from this intermediate, such as prostaglandins and carboxyclic nucleoside analogs, but no process for the synthesis was suggested or attempted because of the difficulty of such a process. Posternak, Th. in Helvetica Chemica Acta 55, 2839 to 2844 (1972) describes the preparation of a racemic mixture of the acetonide protected cyclopentanoid.